Bacterial endotoxins and pathogenesis of Gram-negative infections: current status and future direction

SUMMARY. 100 years after the discovery of a bacterial ’endotoxin’, 50 years after the introduction of anti-biotics and 25 years after the routine use of intensive care units to support septic shock patients, Gram-nega-tive infections continue to account for significant morbidity and mortality. In the coming decade, basic research on the structure/function of LPS, the cytokine cascade, and receptor-mediated intracellular signalling responses to LPS and cytokines will provide a greater understanding of the molecular, cellular and systemic responses to endotoxin and infection. New therapeutic agents now emerging from research, and better de-signed clinical trials to assess those agents will contribute to the next significant decline in sepsis- and shock-related morbidity and mortality. This article summarizes the findings of a workshop convened at the National Institutes of Health (NIH) to examine current research on endotoxin and Gram-negative septic shock. Almost exactly one century ago, Pfeiffer coined the term ’endotoxin ’ to describe a biologically active ma-terial present in culture filtrates of Gram-negative bacte-ria. While early studies allowed this microbial product to be distinguished from most toxins produced by bacte-ria on the basis of its heat stability, detailed chemica